Ontology highlight
ABSTRACT:
PROVIDER: PRJNA564377 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10082820_1.fastq.gz | Fastqsanger.gz | |||
| SRR10082820_2.fastq.gz | Fastqsanger.gz | |||
| SRR10082821_1.fastq.gz | Fastqsanger.gz | |||
| SRR10082821_2.fastq.gz | Fastqsanger.gz | |||
| SRR10082822_1.fastq.gz | Fastqsanger.gz |
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Project description:Retinitis pigmentosa (RP) is an irreversible and inherited retinopathy. RPGR mutations are the most common causes of this disease. It remains challenging to decipher the mechanism of RPGR mutation because of the lack of appropriate study models. The substitution of patient-specific diseased retina without ethical restrictions is desired and iPSC-derived 3D retina is the best choice. In our experiment, we generated iPSCs from one RP patient with 2-bp frameshift mutation in the exon14 of RPGR gene, which were differentiated into retinal organoids. Also we generated iPSCs from a normal control and differentiated those control-iPSCs into healthy retinal organoids. Samples of patient- and control-retinal organoids at W0, W7, W13 (two replicates), W18 (two replicates) and W22 (two replicates for patient) were collected for RNA-seq. Corrected-iPSC were derived from CRISPR/Cas9-mediated gene correction. Then we collected the corrected-iPSC derived retinal organoids at W0, W7, W13 (two replicates), W18 (two replicates) and W22 (two replicates) for RNA-seq. Through the RNA-seq data, we demonstrate that patient-specific iPSC-dervied 3D retinae can recapitulate disease progress of Retinitis Pigmentosa through presenting defects in photoreceptors' gene profile. CRISPR/Cas9-mediated gene correction can rescue photoreceptor gene profile. Those transcriptome are consistent with the phenotype and function.
2020-02-01 | E-MTAB-6490 | biostudies-arrayexpress
Project description:Compare single cell transcriptomes of control and USH1B patient iPSC-derived retinal organoids to elucidate disease mechanisms of Usher syndrome type IB (USH1B). USH1B patient fibroblasts were collected at Great Ormond Street Hospital (GOSH) and reprogrammed to iPSCs. Control and patient iPSCs differentiated in vitro to generate retinal organoids and collected at 35wks. Sequencing was performed at GENEWIZ (Azenta life sciences) on a Illumina NovaSeq system. Data aligned to the human genome UCSC hg38 using cellranger package.
2023-03-27 | E-MTAB-11990 | biostudies-arrayexpress
Project description:To investigate the effects of RHO-CNV in human iPSC-derived retinal organoids. Furthermore Photoregulain3 (PR3) was added to media for 7 days to modulate RHO levels. We then performed gene expression profiling analysis D300+ retinal organoids.
2023-10-22 | GSE245545 | GEO
Project description:Modelling and rescue of RP2 Retinitis Pigmentosa using iPSC Derived Retinal Organoids
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Project description:1-deoxysphinganine accumulation is associated with retinal toxicity. We used single nucelus and bulk sequencing to profile transcriptional remodeling following treatment with 1-dexoysphnganine in human iPSC-derived retinal organoids.
2023-05-30 | GSE213948 | GEO
Project description:To investigate the effects of Notch inhibition at various stages of differentiation of human iPSC-derived retinal organoids. PF03084014 was added to media for 2 days and organoids analyzed 4 weeks later. We then performed gene expression profiling analysis using data obtained from RNA-seq at three stages of differentiation D45, D60 and D90.
2022-09-05 | GSE212640 | GEO
Project description:Mutations in the carboxy terminal of the core spliceosome factor PRPF8 cause autosomal dominant retinitis pigmentosa (RP) 13. Comprehensive cellular, biochemical, and molecular investigations of iPSC-derived retinal organoids, retinal pigment epithelium (RPE) and kidney organoids from four patients carrying the pathogenic PRPF8 RP type 13 c.6926A>C (p.H2309P) heterozygous missense mutation, revealed retinal tissue-specific effects including lower splicing specificity, ciliary abnormalities, altered apical-basal polarity, rod degeneration and loss of photoreceptors. The p.H2309P mutation affected the 5’ splice site recognition by PRPF8 of transcripts encoding ciliary proteins, altered spliceosome kinetics and organisation of nuclear speckles as well as PRPF8 binding to spliceosomal U6 snRNAs and snoRNAs, leading to accumulation of unspliced poly A+ mRNAs specifically in RPE cells and retinal organoids. Together these data provide the most comprehensive characterisation of splicing factor causing RP disease, providing molecular insights into the tissue specificity of pathomechanisms and informing future therapeutic approaches.
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Project description:Mutations in RP2 lead to a severe form of X-linked retinitis pigmentosa (XLRP). RP2 functions as a GTPase activating protein (GAP) for the small GTPase ARL3, which is essential for cilia function and for photoreceptor development and maintenance. The mechanisms of RP2 associated retinal degeneration in humans are poorly understood, and genetically engineered animal models of RP2 XLRP present with differing retinal phenotypes and slow degeneration suggesting potential species differences. Here, we developed CRISPR gene edited isogenic RP2 knock-out (RP2 KO) induced pluripotent stem cells (iPSC) and RP2 patient derived iPSC to produce 3D retinal organoids as a human retinal disease model. The isogenic RP2 KO retinal organoids and two unrelated RP2 patient iPSC lines produced retinal organoids with a defined photoreceptor cell layer (ONL) containing rod and cone photoreceptors. Strikingly the RP2 KO and RP2 patient derived organoids showed a thinning of the ONL by 180 days (D180) of culture, which was associated with a spike in cell death in the ONL at D150 of differentiation. RNA sequencing confirmed induction of cell death pathways in the RP2 null organoids at this stage. Photoreceptor cell death and ONL thinning was attributed to cells undergoing terminal rod cell differentiation characterized by reduced RHO expression and fewer rhodopsin immunoreactive photoreceptors. Gene augmentation with a human RP2 transgene in an AAV2/5 vector efficiently transduced RP2 KO organoids and led to high levels of RP2 expression in both rods and cones. Importantly, the viral transduction significantly increased ONL thickness and restored rhodopsin expression, suggesting rescue of the RP2 degeneration phenotype. These data show that 3D retinal organoids can be used to model molecular defects associated with inherited retinal disease, photoreceptor cell death and also to test potential therapies targeted to prevent photoreceptor degeneration.
2020-07-08 | GSE148300 | GEO
Project description:ABCA7 loss-of-function variants are associated with increased risk of Alzheimer’s disease (AD). Using ABCA7 knockout human iPSC models generated with CRISPR/Cas9, we investigated the impacts of ABCA7 deficiency on neuronal metabolism and function. Lipidomics revealed that mitochondria-related phospholipids, such as phosphatidylglycerol and cardiolipin were reduced in the ABCA7-deficient iPSC-derived cortical organoids. Consistently, ABCA7 deficiency induced alterations of mitochondrial morphology accompanied by reduced ATP synthase activity and exacerbated oxidative damage in the organoids.
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Project description:Subretinal transplantation of human retinal organoid-derived cells can potentially restore vision lost in photoreceptor dystrophies. Prior studies analyzed the maturation, integration, and function of transplanted organoid cells in the subretinal region, but detailed molecular analysis of transplanted photoreceptor and of cells that migrate to other retinal layers has not been conducted. Here, we characterized migratory and non-migratory organoid-derived cells following subretinal transplantation into a dystrophic host. Retinal organoids derived from Crx-tdTomato+ H9 human embryonic stem cells (hESC) (aged D134) were transplanted into immunodeficient Rd1/NS mice. Graft-derived cells using single-cell RNA sequencing and histological analysis were analyzed 4.5 months later. Age-matched human retinal organoids maintained in vitro served as controls. Graft-derived cells migrated to all retinal layers, and underwent long-distance tangential migration. Transcriptomic analysis of transplanted cells identified two cell types not found in cultured controls – PAX2-positive retinal astrocytes, and ARX/NKX2-2/HOXC8-positive brain/spinal cord-like neural precursors. Some migrating cells were proliferative, but overall less proliferation was observed in the transplants than the cultured organoids. Transplanted rod and cone photoreceptors remained in the subretinal space, and were more mature than age-matched photoreceptors in cultured organoids. This study shows that extrinsic signals present in the degenerative subretinal space promote maturation of photoreceptors in transplanted retinal organoids, while also inducing formation of migratory cell populations that are not normally derived from retinal progenitors, either in cultured organoids or in vivo. This has important implications for the design and safety of cell-based therapies for treating photoreceptor dystrophies.
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